Biomedical subjects
Publications and source records attributed to C Johnson.
The author presents an overview of benign breast disease. History, epidemiology, risk factors, hormonal influence, and clinical features are discussed. Appropriate treatment for mastalgia, diffuse nodularity, mastitis, and dominant lumps is presented. The importance of patient education, clinical breast examination, mammography, and patient reassurance is stressed. Benign breast disease in men is also discussed.
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The abnormal adherence of sickle red blood cells (SS RBC) to endothelial cells has been thought to contribute to vascular occlusion, a major cause of morbidity in sickle cell disease (SCD). We determined whether the interaction of SS RBC with cultured endothelial cells induced cellular oxidant stress that would culminate in expression of cell adhesion molecules (CAMs) involved in the adhesion and diapedesis of monocytes and the adherence of SS reticulocytes. We showed that the interaction of SS RBC at 2% concentration in the presence of multimers of von Willebrand factor (vWf), derived from endothelial cell-derived conditioned medium (E-CM) with cultured human umbilical vein endothelial cells (HUVEC), resulted in a fivefold increased formation of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-kB, both indicators of cellular oxidant stress. Normal RBC show none of these phenomena. The oxidant stress-induced signaling resulted in an increased surface expression of a subset of CAMs, ICAM-1, E-selectin, and VCAM-1 in HUVEC. The addition of oxygen radical scavenger enzymes (catalase, superoxide dismutase) and antioxidant (probucol) inhibited these events. Additionally, preincubation of HUVEC with a synthetic peptide Arg-Gly-Asp (RGD) that prevents vWf-mediated adhesion of SS RBC reduced the surface expression of VCAM-1 and NF-kB activation. Furthermore, SS RBC-induced oxidant stress resulted in a twofold increase in the transendothelial migration of both monocyte-like HL-60 cells and human peripheral blood monocytes, and approximately a sixfold increase in platelet-endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation, each of which was blocked by protein kinase C inhibitor and antioxidants. These results suggest that the adherence/contact of SS RBC to endothelial cells in large vessel can generate enhanced oxidant stress leading to increased adhesion and diapedesis of monocytes, as well as heightened adherence of SS reticulocytes, indicating that injury/activation of endothelium can contribute to vaso-occlusion in SCD.
Saccharomyces cerevisiae csg2Delta mutants accumulate the sphingolipid inositolphosphorylceramide, which renders the cells Ca2+-sensitive. Temperature-sensitive mutations that suppress the Ca2+ sensitivity of csg2Delta mutants were isolated and characterized to identify genes that encode sphingolipid synthesis enzymes. These temperature-sensitive csg2Delta suppressors (tsc) fall into 15 complementation groups. The TSC10/YBR265w gene was found to encode 3-ketosphinganine reductase, the enzyme that catalyzes the second step in the synthesis of phytosphingosine, the long chain base found in yeast sphingolipids. 3-Ketosphinganine reductase (Tsc10p) is essential for growth in the absence of exogenous dihydrosphingosine or phytosphingosine. Tsc10p is a member of the short chain dehydrogenase/reductase protein family. The tsc10 mutants accumulate 3-ketosphinganine and microsomal membranes isolated from tsc10 mutants have low 3-ketosphinganine reductase activity. His6-tagged Tsc10p was expressed in Escherichia coli and isolated by nickel-nitrilotriacetic acid column chromatography. The recombinant protein catalyzes the NADPH-dependent reduction of 3-ketosphinganine. These data indicate that Tsc10p is necessary and sufficient for catalyzing the NADPH-dependent reduction of 3-ketosphinganine to dihydrosphingosine.
BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a rapid response transcription factor for genes whose products are critical for inflammation and immunity. In a rat model of heterotopic cardiac transplantation, we studied NF-kappaB DNA binding activity and nitric oxide (.NO) production in untreated allografts and whether inhibition of NF-kappaB suppresses .NO production and prolongs graft survival. METHODS: In allograft recipients and isograft controls, NF-kappaB was assayed by electrophoretic mobility shift assay, daily from transplant until rejection. Myocardial .NO was directly detected in explanted allografts by electron spin resonance spectroscopy on day 6 after transplant. The potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC; 250 mg/kg s.c.) was administered daily from transplant until day of rejection. The extent of graft lymphocytic infiltrate was assessed by routine hematoxylin and eosin staining. Immunohistochemical staining of NF-kappaB was per formed to identify the cell type responsible for NF-kappaB activity. RESULTS: A time-dependent increase in myocardial NF-kappaB activity was seen in untreated allografts as compared with isografts as determined by PhosphorImage analysis. Peak NF-kappaB activity occurred in allografts on day 4 with a ninefold increase as compared with isografts (24.0+/-3.7% vs. 2.7+/-0.5; P<0.05). On posttransplant day 6, electron spin resonance spectroscopy analysis of allografts demonstrated .NO identified by a triplet nitrogen signal centered at g=2.012 with hyperfine splitting of 17.5 Gauss, which is consistent with nitrosoheme formation and low-field signals at g=2.08 and g=2.03 consistent with nitrosomyoglobin. These signals were not seen in native hearts of allograft recipients. With PDTC administration, a threefold decrease in NF-kappaB activity within the transplanted heart was observed on posttransplant day 5 as compared with untreated allografts (9.7+/-1.6% vs. 23.5+/-2.5%; P<0.01). PDTC prolonged graft survival as compared with untreated allografts (11.7+/-0.3 vs. 6.6+/-0.2 days; P<0.05) and reduced the intensity of the nitrosoheme and nitrosomyoglobin signals. Allograft mononuclear cell infiltrate correlated with peak NF-kappaB activity with peak infiltrate on posttransplant day 4. PDTC treatment had no effect on the extent of infiltrate. Immunohistochemical staining localized NF-kappaB to the infiltrating mononuclear cells on posttransplant day 5. CONCLUSION: These data support a role for NF-kappaB in allograft rejection.
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This study investigated cardiac autonomic function in patients with panic disorder and normal controls using Holter ECG records. A decrease in ultra-low frequency power (< 0.0033 Hz) is known to be associated with an increased risk for cardiovascular mortality in humans. Twenty-four-hour ECG was recorded in 29 patients with panic disorder and 23 normal controls using Holter records. Data for 20 h and also 20000 s of awake and 20000 s of sleep periods were analyzed using spectral analysis to quantify absolute and relative heart-period variability in ultra low (ULF: < 0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. The patients with panic disorder had significantly lower total and absolute ULF power, which was more pronounced during sleep. The patients also had significantly lower relative ULF power and significantly higher relative LF power during sleep. There was a significant increase of relative LF power from awake to sleep period only in the patient group. The decrease in total and ULF power may increase the risk of mortality and sudden arrhythmic death in patients with panic disorder if they experience a cardiac event. The higher relative LF power during sleep also suggests a possible higher sympathetic drive in the patients during sleep.
Previous investigators have reported the presence of two dominant proteins, tectonin I (25 kDa) and tectonin II (39 kDa), in nuclei and nuclear matrix from plasmodia of Physarum polycephalum. We demonstrate, by a modification of the nuclear isolation protocol and by protease sensitivity, that the tectonins are not nuclear proteins but rather are located on the exterior surface of the plasma membrane. We report the sequences of cDNAs of tectonins I and II, which encode 217 and 353 amino acids, respectively. Tectonin I is homologous to the C-terminal two-thirds of tectonin II. Both proteins contain six tandem repeats that are each 33-37 amino acids in length and define a new consensus sequence. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. Tectonin II has an additional N-terminal domain that includes a 47-residue sequence highly similar to the galactoside-binding sequence of the B-chain of ricin. The tectonins may be lectins that function as part of a transmembrane signaling complex during phagocytosis.
BACKGROUND: 5-Fluorouracil (5-FU), as a single agent, produces a 15% response rate in advanced squamous cell carcinoma of the head and neck (SCCHN). N-phosphonacetyl-L-aspartate (PALA) inhibits pyrimidine biosynthesis and increases incorporation of 5-FU metabolites into ribonucleic acid (RNA). Recombinant alpha interferon-2b (rIFN-alpha-2b) may inhibit 5-FU clearance and blunt reflex rise in thymidylate synthetase, therefore enhancing inhibition of the target enzyme of 5-FU. METHODS: In an attempt to exploit their potential therapeutic synergy, we initiated a phase II trial combining PALA 250 mg/m2 by intravenous (IV) bolus day 1 with 5-FU 2600 mg/m2 24-hour IV infusion initiated 24 hours after PALA, followed by rIFNalpha-2b 10 million units (MU) by subcutaneous injection days 2, 3, and 4 in patients with advanced, measurable SCCHN incurable with surgery or radiotherapy. Treatment was repeated weekly; patients were assessed every 4-6 weeks. Pretreatment tumor specimens were analyzed for p53 mutations in exons 5-8 and for protein expression using the p53 polyclonal antibody CM-1. RESULTS: Nineteen patients were enrolled from November 1991 through February 1994. Median age was 59 years (range, 31-72 years). All had previously received definitive radiotherapy, and all but two had undergone surgical resection. Seven patients (37%) had received prior adjuvant chemotherapy. Median time from initial diagnosis to protocol enrollment was 17 months (range, 5 months to 10 years). Median performance status (PS) was 1. Primary tumor sites included oral cavity (8 patients), larynx (7 patients), oropharynx (3 patients), and hypopharynx (1 patient). The median serum transferrin was 241 (range, 141-333). Sixteen patients (84%) had sufficient pretreatment biopsy material for p53 analysis. Patients received a median of 6 weeks of treatment (range, 2-30 weeks). Six patients (32%) in the absence of disease progression failed to finish the first 6 weeks of treatment: 3 died of pulmonary insufficiency or pneumonia and 3 were removed from study during the first 6 weeks due to toxicity. Grade 2-3 flulike symptoms occurred in 17 patients (89%); grade > or = 3 fatigue occurred in 12 patients (63%), and grade > or = 2 stomatitis occurred in 5 (26%). Gastrointestional toxicity was minimal and myelosuppression mild. Of 13 evaluable patients, there were 2 partial responses (15%) lasting 3 months and 20 months; 5 patients with stable disease lasting 2, 2, 2.5, 3, and 4.5 months; and 6 with disease progression. For all 19 patients, the overall response rate was 11%, the median survival was 6 months and 1-year survival rate 26%. Lower transferrin values (< or =241) were associated with shortened median survival 2.5 vs 11 months). Increased p53 protein expression but not p53 mutations in pretreatment specimens also predicted inferior survival (median, 6 vs 11 months) after enrollment in study (p = .0124). CONCLUSIONS: Biochemical modulation of 5-FU by rIFNalpha-2b and PALA does not enhance its efficacy in patients with advanced SCCHN whose disease has progressed after prior radiotherapy. Serum transferrin and p53 protein expression segregate outcome in this group of uniformly treated patients.
Several natural isolates of Bacillus thuringiensis have been found which are active against larvae of Musca domestica, the housefly, as well against larvae of the family Calliphoridae. The toxicity is attributed to the Cry IB class of protoxin. Presolubilization of the toxin was not necessary to induce mortality in any of the insect species assayed. The addition of spores to the delta-endotoxin was, however, essential to inducing significant mortality in larvae of Chrysomya albiceps (Weid.) and enhanced mortality in the other species tested. Copyright 1998 Academic Press.
BACKGROUND & AIMS: Chronic tissue injury in the esophagus associated with gastroesophageal reflux disease may result in sensitization of afferent pathways mediating mechanosensitivity and chemosensitivity. The aim of this study was to evaluate the sensitivity to intraluminal acid and to distention of the esophagus in patients with mild-to-moderate gastroesophageal reflux disease. METHODS: Perceptual responses to intraluminal acid perfusion and to esophageal distention and pressure volume relationships were evaluated in 10 healthy volunteers and in 11 patients. Mechanosensitivity was evaluated with a barostat using unbiased distention protocols and verbal descriptor ratings of sensations. Chemosensitivity to acid was determined at baseline and after a 1-month treatment of acid suppression. RESULTS: Patients showed enhanced perception of acid perfusion but not of esophageal distension. Chemosensitivity but not mechanosensitivity was correlated with reflux symptoms and with the degree of endoscopically shown tissue injury at baseline. Tissue injury was not associated with altered compliance. CONCLUSIONS: Mild-to-moderate chronic tissue injury in gastroesophageal reflux disease differentially affects mechanosensitive and chemosensitive afferent pathways. Chronic acid reflux by itself is not likely to play a role in reported esophageal hypersensitivity to distention in patients with noncardiac chest pain.
BACKGROUND & AIMS: Evaluation of new patients with noncardiac chest pain (NCCP) may require a variety of costly tests. The aim of this study was to evaluate the efficacy of the omeprazole test (OT) in diagnosing gastroesophageal reflux (GERD) in patients with NCCP and estimate the potential cost savings of this strategy compared with conventional diagnostic evaluations. METHODS: Thirty-nine patients referred by cardiologists were enrolled. Baseline symptoms were recorded, and the patients were randomized to either placebo or omeprazole (40 mg AM and 20 mg PM) groups for 7 days. Patients were crossed over to the other arm after a washout period and repeat baseline symptom assessment. All patients underwent 24-hour esophageal pH monitoring and upper endoscopy before randomization. RESULTS: Thirty-seven patients (94.9%) completed the study. Twenty-three (62.2%) were classified as GERD positive and 14 as GERD negative. Eighteen (78%) GERD-positive patients and 2 (14%) GERD-negative patients had a positive OT (P < 0.01), yielding a sensitivity of 78.3% (95% confidence interval, 61.4-95.1) and specificity of 85.7% (95% confidence interval, 67.4-100). Economic analysis showed that the OT saves $573 per average patient evaluated and results in a 59% reduction in the number of diagnostic procedures. CONCLUSIONS: The OT is sensitive and specific for diagnosing GERD in patients with NCCP. This strategy results in significant cost savings and decreased use of diagnostic tests.
BACKGROUND: Previous studies by our group have identified a 23% prevalence of intestinal metaplasia involving the gastric cardia in patients undergoing elective esophagogastroduodenoscopy (EGD). The current study evaluates the potential clinical utility of vital staining with methylene blue for detecting intestinal metaplasia of the cardia. In addition, the prevalence of Helicobacter pylori infection and incidence of dysplasia in cardia intestinal metaplasia was assessed. METHODS: Twenty-four of 104 patients undergoing elective EGD were previously identified with cardia intestinal metaplasia. Twenty-one of these 24 returned for follow-up EGD with methylene blue staining and cardia biopsies. During EGD four random biopsies were taken in the cardia. After staining with methylene blue, four targeted biopsy specimens were taken from any stained areas. H. pylori infection was assessed by rapid urease testing and serologic evaluation. RESULTS: Staining with methylene blue was positive in 16, equivocal in 4, and negative in 1. Overall, cardia intestinal metaplasia was identified in 17 of 21 patients (81%) by at least one of the 8 biopsies. The sensitivity of detecting intestinal metaplasia by targeted biopsies to stained areas was 67% as opposed to 38% for random biopsies (odds ratio 3.0: 95% CI [0.88,10.24]). The prevalence of H. pylori infection in patients with cardia intestinal metaplasia was 76%. One patient developed low-grade dysplasia, whereas the others remained negative. CONCLUSIONS: Intestinal metaplasia of the gastric cardia is associated with a high prevalence of H. pylori infection and is a reproducible finding in the majority of patients. Methylene blue staining and an increasing number of biopsies improve the sensitivity of detecting this potentially neoplastic lesion.
RATIONALE AND OBJECTIVES: The authors examined the prognostic value of magnetic resonance (MR) imaging in stress injuries of bone. MATERIALS AND METHODS: Clinical follow-up data were collected in 35 patients who underwent MR imaging because of suspected stress fractures. MR findings were correlated with total duration of symptoms, the time to return to sports activity, and findings at follow-up radiography. RESULTS: The MR imaging finding of a "fracture" or "fatigue" line or a cortical signal intensity abnormality was predictive of a longer symptomatic period, whereas muscle edema was predictive of a shorter symptomatic period. A published grading system could be used in only 24 patients; the MR imaging grade of injury did not show correlation with clinical outcome. CONCLUSION: The MR imaging finding of either a medullary line or a cortical abnormality appears to indicate a more severe stress injury of bone. A previously published MR imaging grading system for stress injuries of the tibia was not prognostic in this more heterogeneous patient group.
Barrett's esophagus (BE) is considered to be a disease of white males with a prevalence ranging from 0.5 to 4.0% in patients undergoing upper endoscopy (EGD) for any indication, and from 12 to 15% in patients with gastroesophageal reflux disease (GERD). The prevalence of BE in Hispanics is not known, but it is assumed to be lower. The aims of this study were to determine the prevalence of BE in Hispanic patients and to compare demographic and endoscopic characteristics with Caucasian patients with BE. Records of patients undergoing an EGD between October 1993 and October 1996 were retrospectively reviewed. Patients were included in the study only if they had columnar-appearing esophageal mucosa at endoscopy and intestinal metaplasia with Alcian blue-staining goblet cells on biopsy. An extensive chart review was performed in patients with BE. There were 75 new cases of BE discovered: 60 (80%) were Caucasians, 6 (8%) Hispanics, 1 (1.4%) Native American, and 8 (10.6%) patients with either unknown or unconfirmed ethnicity. Of the 75 patients, 74 male, and the mean age was 65 +/- 11.4 years (range 36-92 years). The prevalence of BE in Caucasians and Hispanics undergoing EGD for any reason was similar (5.3% and 3.8%, respectively, P = 0.563). The prevalence of BE in patients presenting with GERD symptoms was also similar between Caucasians and Hispanics (25% and 16%, respectively, P = 0.304). The two groups did not differ significantly with respect to age, symptoms, habits, or endoscopic findings. In conclusion, the prevalence of BE among Hispanic patients is similar to Caucasian patients, an unexpected finding.
Little is known about the variables that might be associated with posttraumatic stress symptomatology in high-risk occupational groups such as professional firefighters and paramedics. A sample of 173 urban professional firefighter/EMT's and firefighter/paramedics rated and ranked the stressfulness of 33 actual and/or potential duty-related incident stressors. They also reported whether they had experienced each of these incident stressors within the past 6 months and, if they had, to recall on how many occasions within the past 6 months. A principal components analysis of their rescaled incident stressor ratings yielded five components: Catastrophic Injury to Self or Co-worker, Gruesome Victim Incidents, Render Aid to Seriously Injured, Vulnerable Victims, Minor Injury to Self and Death & Dying Exposure.
This study assessed the efficacy of a 10-week broad-spectrum intervention offered to bereaved parents about 4 months after the deaths of their 12--28-year-old children due to accidents, homicide, or suicide. For three outcomes of distress there was a significant interaction between treatment and baseline values for each outcome for mothers both immediately posttreatment and 6 months later. The intervention appeared to be the most beneficial for mothers most distressed at baseline. Fathers showed no immediate benefits of treatment. Further research is needed to investigate these unexpected results for fathers and to further characterize those who benefit from similar programs.
This article analyzes the organizational structures of 155 medical group practices providing services in the highly competitive managed care environment in the upper midwest. The structure of the group practices and the methods of physicians' payment are analyzed in terms of the proportion of revenue obtained from financial risk-sharing managed care payment systems and the length of time involved with those systems.